Splenomegaly : Examination techniques and Clinical Approach

ANATOMY OF SPLEEN

• Location: Left hypochondrium
• Rule of odds (1,3,5,7,9-11):
  • 1 inch thick
  • 3 inches broad
  • 5 inches long
  • 7 ounces weight
  • underlies 9-11 ribs
• Position: obliquely along long axis of 10^th rib; directed downward, forward and laterally
• Arterial supply: Splenic artery from celiac trunk
• Venous drainage: Splenic vein → Portal vein
• Lymphatic drainage: Celiac (Para-aortic) nodes
• Nerve supply: Sympathetic from celiac plexus

Histologically:

• Red pulp: sinuses lined by endothelial macrophages and cords (spaces)
• White pulp: structure similar to lymphoid follicles

FUNCTIONS OF SPLEEN

Spleen is the largest lymphoid organ organ and serves following functions –

1. Red pulp: Removal of senescent and defective RBCs (mechanism: hypoxia, low pH and low glucose)
2. White pulp: Synthesis of antibodies
3. Removal of antibody-coated bacteria and anti-body coated blood cells from circulation
4. Extramedullary hematopoiesis
5. Blood pooling

An increase in these normal functions may result in splenomegaly

EXAMINATION OF SPLEEN

1. Palpation:

• Right hand: Keep hand still and ask patient to take a deep breath through the mouth to feel spleen edge being displaced downwards. Move hand up diagonally from right iliac fossa, towards left upper quadrant on expiration.
• Left hand: Place the hand around patient’s lower ribs and approach costal margin to pull spleen forward

If history suggest splenomegaly but is not palpable: Roll the patient on to the right lateral position with flexion of left hip and knee and examine as before.

Splenomegaly: Abnormal enlargement of Spleen

If ascites is gross: Use dipping method to palpate the spleen

2. Percussion:

• Examine the spleen with the patient holding the breath during full inspiration; percuss both below and then above the left costal margin
• Percuss from resonance to dullness

Castell’s sign: With the patient supine, percussion in the lowest intercostal space in the anterior axillary line (8th or 9th) produces a resonant note if the spleen is normal in size. This is true during expiration or full inspiration. A dull percussion note on full inspiration suggests splenomegaly.

MECHANISMS OF SPLENOMEGALY

1. Work hypertrophy

• Reticuloendothelial system hyperplasia (Removal of defective erythrocytes)
• Immune hyperplasia (Response to infection or disordered immunoregulation)
• Extramedullary hematopoiesis (Bone marrow disorder)

2. Infiltration

• Acellular deposition: Metabolic disorders
• Cellular deposition: Neoplasia

3. Passive congestion

CAUSES OF SPLENOMEGALY

Mnemonic: CHIMPS

1. Congestive: Portal hypertension (Cirrhosis, Hepatic/Splenic/Portal vein occlusion), Cardiac (CHF, Constrictive pericarditis)
2. Hematologic: Neoplastic (Lymphomas, Leukemias, Myeloproliferative disorders), Non-neoplastic (Megaloblastic anemia, Hemoglobinopathies, Autoimmune hemolytic anemias)
3. Infective: Subacute Bacterial Endocarditis (SBE), Brucellosis, TB, Salmonella, Septic shock, Infectious mononucleosis, Hepatitis, Cytomegalovirus (CMV), Histoplasmosis, Malaria, Leishmaniasis, Schistosomiasis, Trypanosomiasis
4. Inflammatory: Felty’s syndrome, SLE, Rheumatoid arthritis, Sarcoidosis
5. Metabolic-infiltrative: Gaucher’s disease, Niemann-Pick’s syndrome, Amyloidosis
6. Miscellaneous: Cyst, abscess, cavernous hemangiomas
7. Primary hypersplenism: Dacie’s syndrome (Splenomegaly of unknown cause + Pancytopenia)
8. Splenic cyst or hamartoma

Felty’s syndrome: A triad of Rheumatoid arthritis, Splenomegaly and Neutropenia

Hypersplenism: It is the splenic hyperactivity with increased blood cell destruction. Diagnostic criteria are:

• Splenomegaly
• Pancytopenia
• Normal bone marrow (Primary) or Hypercellular bone marrow (secondary)
• Reversibility by splenectomy

Banti’s disease: Congestive splenomegaly with hypersplenism occuring in cirrhosis and portal hypertension

CLINICAL APPROACH TO SPLENOMEGALY

A) History:

1. Suggestive of splenomegaly:

• Pain and a heavy sensation in LUQ radiating to back
• Radiation to left shoulder tip in splenic infarction
• Early satiety in massive splenomegaly

2. Suggestive of associated disease:

• B symptoms i.e. Fever, night sweats, or weight loss (Neoplastic, SBE and other infections)
• Bone pain (AML, Sickle cell disease, Gaucher’s disease)
• Fatigue, dyspnea, bruising and/or petechiae (Hemolytic)
• Joint pains (RA, SLE)
• Pruritus (Hodgkin lymphoma, Polycythemia)
• Epigastric or generalized abdominal pain (Splenic vein thrombosis eg. Pancreatitis)
• Cough and dyspnea (Sarcoidosis)
• History of alcoholism, liver disease (Liver cirrhosis)
• History of Pancreatitis (Splenic vein thrombosis)
• Personal or family history of hemoglobinopathy, lysosomal storage disorder, rheumatoid arthritis
• History of neonatal umbilical vein sepsis (Portal vein thrombosis)
• Recent infections including malaria
• History of recent dental work or blood transfusions (SBE)
• Recent abdominal trauma

B) Physical examination:

1. Inspection: Fullness in LUQ that descends on inspiration (massive splenomegaly)

2. Palpation: Spleen is not normally palpable (palpable when 2-3 times enlarged). Enlargement takes place in a superior and posterior direction before it becomes palpable subcostally. A palpable spleen must be reported in following points:

• Degree of enlargement: Measured below from the left costal margin along the splenic axis in centimeters/inches or number of fingers
• Splenic notch: Felt on its lower medial border
• Margin: Usually sharp
• Consistency: Soft, firm or hard
• Tenderness: Tender or non-tender
• Surface: Smooth or irregular
• Movement with respiration: Always moves downwards and medially with respiration
• Fingers insinuation: cannot get between spleen and ribs
• Palpable splenic rub: Present or not

A palpable spleen is distinguished from palpable left kidney mass by:

• Not bimanually palpable and not ballotable
• Upper border cannot be felt
• Notch on lower medial border
• Fingers cannot get between spleen and ribs
• Dull on percussion

Normal sized spleen may be palpable in:

• Chronic Emphysema
• Low diaphragm

3. Auscultation: Venous hum or a friction rub may be heard

4. Percussion: Palpation is confirmed by dullness as spleen is dull to percussion

5. Other relevant findings in Physical Examination:

a. Skin:

• Pallor: Chronic malaria, Chronic kala-azar, Leukemia, Lymphomas, Cirrhosis, Hemolytic anemia, Hypersplenism
• Icterus: Hemolysis (Hemolytic anemias, Acute malaria, Lymphoma), Budd-Chiari syndrome (Hepatic vein obstruction), Chronic liver disease
• Periorbital purpura: Amyloidosis
• Plethora: Polycythemia vera
• Skin infiltration and masses: AML or ALL
• Butterfly rash: SLE
• Janeway lesion: SBE
• Erythema nodosum, lupus pernio: Sarcoidosis
• Spider naevi and palmar erythema: Portal HTN due to chronic liver disease
• Hemorrhagic spots: Acute leukemia, SBE, SLE, ITP, Felty’s syndrome, Blast crisis of CML or CLL

b. Lymphadenopathy:

• Autoimmune disorders: RA, Felty’s syndrome, SLE, Sarcoidosis
• Infection: Infectious Mononucleosis, AIDS, Toxoplasmosis, CMV, Disseminated TB
• Neoplasm: Lymphomas and Leukemias

c. Fever

• Infections: Malaria, Kala-azar, Enteric fever, SBE, Miliary TB, Acute viral hepatitis
• Neoplasm: Acute leukemias, CML, Lymphoma
• Collagen vascular diseases

d. Eyes and ENT

• Suffused conjunctiva: Polycythmia vera
• Fundoscopy: Roth spots (SBE), Choroidal tubercle (Miliary TB)
• Pharyngitis: EBV infection
• Macroglossia, Jugula vein distension or Periorbital edema: Amyloidosis
• Mongoloid facies: Thalassemia

e. Cardiac examination:

• New or changing murmurs: SBE

f. Extremities:

• Digital ischemia/gangrene or thrombosis: Essential thrombocytosis
• Joint deformities: RA, Felty’s syndrome, SLE
• Lower extremity edema: Amyloidosis

g. Abnormal neurological examination:

• Essential thrombocytosis
• Non-Hodgkin’s lymphoma (NHL)

Differential diagnosis of splenomegaly:

1. Enlarged left kidney
2. Enlarged left lobe of liver
3. Carcinoma of stomach
4. Carcinoma of splenic flexure of colon
5. Omental mass (TB or malignancy)
6. Malignancy of tail of pancreas
7. Ovarian tumor in females

C) Grading of Splenomegaly Based on Degree of Enlargement

1. Massive (>8cm or >5 fingers):

• Chronic Myeloid Leukemia (CML)
• Myelofibrosis
• Chronic Malaria, Chronic Kala-azar
• Gaucher’s disease

Tropical Splenomegaly Syndrome or Hyperactive Malarial Splenomegaly (HMS)

An idiopathic splenomegaly affecting malnourished children and adult ♀ in malaria-endemic regions eg. New Guinea, Africa, which may be a defective immune response to P malariae

• Clinical: Massive splenomegaly, asthenia, fatigue
• Lab: ↑ IgM antibodies against Plasmodium, ↓ T-helper cells ↓ CD4:CD8 ratio

2. Moderate (4-8cm or 2-4 fingers):

• Causes of massive splenomegaly
• Hemolytic anemia
• Portal hypertension
• Lymphoproliferative disorders: Lymphoma, CLL

3. Mild (<4cm or <2 fingers):

• Causes of moderate splenomegaly
• Infectious hepatitis
• Infectious mononucleosis (IM)
• Subacute Bacterial Endocarditis (SBE)
• Idiopathic Thrombocytopenic Purpura (ITP)
• Amyloidosis
• Sarcoidosis
• Felty’s syndrome

D) Lab Investigations:

1. Initial investigations:

• FBC with differential count
  • Leucocytosis: Pyogenic infections, Leukemia
  • Leucopenia: Malaria, Kala-azar, Enteric fever, Felty’s syndrome
  • Pancytosis: Polycythemia
  • Pancytopenia: Hypersplenism
• ESR
  • Increased: Infection, SLE, lymphoma, severe anemia
  • Decreased: Polycythemia
• Peripheral Blood Smear (PBS)
  • Cell morphology: Leukemia, Hereditary spherocytosis, Thalassemia
  • Parasites: Malaria, Kala-azar
• Reticulocyte count (Anemic patients)
  • Increased: Hemolytic anemias
• Blood cultures (Febrile patients)
  • SBE, Enteric fever
• Liver function tests
  • Hyperbilirubinemia: Hemolytic anemias, Other hemolytic conditions, Hepatitis, Chronic liver disease

2. Additional investigations: Based on disease suspected by clinical and/or initial laboratory findings

• Hemoglobin electrophoresis (↑HbF in B-thalssemia)
• Coomb’s test (+ve in autoimmune hemolysis and -ve in hereditary spherocytosis)
• Red cell enzyme testing (G6PD deficiency)
• Osmotic fragility testing (+ve in Hereditary spherocytosis)
• Flow cytometry for lymphoproliferative profile (CLL, Hairy cell leukemia, lymphomas)
• Erythropoietin level (↓ in Polycythemia vera)
• Coagulation test (Chronic liver disease, DIC in AML, SLE)
• Serum lipase and amylase (Pancreatitis)
• Serum LDH (NHL, AML)
• Serum iron (↑ in Hemochromatosis, Thalassemia)
• Paul-Bunnell test (Infectious Mononucleosis)
• Congo red test (Amyloidosis)
• Serum ACE (Sarcoidosis)
• Napier’s Aldehyde test (Chronic Kala-azar)
• Anti-nuclear antibodies (SLE)
• Rheumatoid factor (RA, Felty’s syndrome)
• HBsAg (Hepatitis)
• Rose-Waaler test (Felty’s syndrome)
• Glucocerbrosidase activity (Gaucher’s disease)
• Sphingomyelinase (Niemann-Pick disease)
• Mantoux skin test (TB)
• Kveim skin test (Sarcoidosis)

3. Bone marrow aspiration and biopsy

• Myeloproliferative diseases
• Lymphomas
• Immunological diseases (Sarcoidosis, SLE, Felty’s syndrome, Amyloidosis)
• Gaucher’s disease

4. Lymph node biopsy

• Tuberculosis
• Sarcoidosis
• Lymphoma

5. Splenic biopsy

• Diagnosis of Lymphoma
• Niemann Pick’s disease (Large foamy cells)
• Amyloidosis (Large hyaline masses)

6. Liver biopsy

• Alcohol induced liver disease
• Hepatic steatosis
• Hemochromatosis),

7. Lung or Skin biopsy

• Sarcoidosis

E) Imaging:

1. To evaluate splenomegaly

• Ultrasonography
• CT scan
• Splenoportography
• Spleen liver colloid scan
• MRI
• Angiography

2. Confirming suspected diagnosis

• Chest X-ray:
  • Miliary TB
  • Lymphoma
  • Sarcoidosis
  • Extramedullary hematopoiesis in thalassemia
• Bone X-ray:
  • Mosaic pattern in small bones of hand: Thalassemia
  • Increased bone density: Myelofibrosis or Myelosclerosis
  • Erlenmeyer flask sign in distal femur: Gaucher’s disease
• Skull X-ray:
  • ‘Hair on end‘ appearance in Thalassemia

Investigations should be based on disease suspected by clinical and/or initial laboratory findings

SPLENECTOMY

1. Indications:

• Hodgkin’s lymphoma (for staging the extent of disease)
• Massive splenomegaly (for control of symptoms)
• Traumatic or Iatrogenic splenic rupture (for disease control)
• Hypersplenism or Immune-mediated destruction of one or more blood cell line (for correction of cytopenias)

Causes of Splenic rupture

• Trauma
• Infectious mononucleosis
• Leukemias
• Myelofibrosis
• Congestive splenomegaly

2. Problems after splenectomy:

• Immediate: Increased platelet count may lead to thromboembolic phenomenon
• Long-term: Increased risk of infection with capsulated organisms (like Streptococcus pneumoniae, Nisseria meningitidis, H.influenzae or E.coli), malarial parasites, babesia

Causes of Asplenism or Hyposplenism

• Asplenia: Dextrocardia
• Surgical: Splenectomy
• Diminished function: Sickle cell disease, Celiac disease, Dermatitis herpetiformis with enteropathy

3. Prophylaxis for Post-splenectomy infection:

• Vaccinate 2-3 weeks before elective splenectomy: Pneumococcal vaccine, Hemophilus influenza type B (Hib) vaccine, Meningococcal group C vaccine, Influenza vaccine
• Lifelong Antibiotic prophylaxis: Long-term penicillin V 500mg 12 hourly (erythromycin if allergic to penicillin)
• Revaccination of pneumococcal vaccine: in every 5 years and influenza vaccine anually
• Antimalarial chemoprophylaxis: if needed (travel to endemic area)

4. Post splenectomy hematological features:

• Thrombocytosis: persists in 30% cases
• WBC count: usually normal but there may be mild lymphocytosis and monocytosis
• Red cell morphology: Howell-Jolly bodies (Nuclear remnants), Pappenheimer bodies (contain sideroblastic granules), Heinz bodies (Denatured hemoglobin), Target cells, Nucleated erythrocyte (occasionally)

Sources:

1. Harrison’s Principle of Medicine 16th Edition
2. Davidson’s Principle and Practice of Medicine 20th Edition
3. Bedside Clinics in Medicine Part I by Arup Kumar Kundu
4. Kumar and Clarke’s Clinical Medicine 6th Edition
5. Assessment of Splenomegaly – BMJ Best Practices